Journal Article

Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies

Burger, Jan A, Estrov, Zeev, Ferrajoli, Alessandra, Jain, Nitin, Borthakur, Gautam, Wierda, William G, Daver, Naval, Jabbour, Elias, Strati, Paolo, Keating, Michael J, Thompson, Philip A, Kadia, Tapan M, Peterson, Christine B, Jorgensen, Jeff, Susan M O’Brien, DiNardo, Courtney D

2018

Overview

Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end of therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10−4). Eighteen percent of patients had U-MRD after C3 and 48% at EOT. U-MRD status at EOT was associated with longer PFS (median NR vs 38 mo, p < 0.001). MRD level (≤1% vs >1%) after C3 predicted greater likelihood of U-MRD status at EOT (64% vs 9%, p < 0.001). PFS was significantly longer for patients with MRD ≤1% vs >1% after C3 (median 73 mo vs 41 mo, p < 0.001), but similar for <0.01% vs 0.01–1%. Interim MRD status may therefore be used for risk stratification and to individualize therapy. Eighty-five patients with U-MRD status at EOT had yearly blood MRD monitoring; MRD re-emerged in 38/85, a median of 48 mo after EOT and preceded clinical progression by a median of 24 months, which may allow development of early intervention strategies.

• Publisher: Nature Publishing Group
• Subject: Bone marrow / Chronic lymphocytic leukemia / Color sensitivity / Flow cytometry / Medical treatment / Minimal residual disease / Monitoring / Patients / Therapy